The burden of breast cancer in American women is striking. In the United States alone, it is the most common non-skin cancer in women and the second leading cause of female cancer mortality. The long-term objective of this research is to advanced the frequency and accuracy with which breast cancer can be detected and diagnosed by developing and evaluating imaging method alternatives to x-ray mammography. This goal is motivate by the fact that the detection of breast cancer at an early stage increases the likelihood of successful treatment and long term survival, and yet, is underscored by the recognition that while x-ray mammography is effective and likely to remain as the primary imaging modality for asymptomatic screening, it is not very specific in the differentiation of benign from malignant abnormalities nor is it very sensitive under certain clinical conditions. The immediate focus of the proposed five year Program is to (1) demonstrate the clinical feasibility of four quantitative physical property-based breast tissue imaging strategies which have been identified, and (2) initiate the clinical evaluation of these imaging schemes in a common cohort of patients with normal and diseased breasts. Specifically, Project I will exploit potential differences in the elastic properties of breast malignancy deduced from vibrationally- induced volumetric magnetic resonance phase and displacement data coupled to elastodynamic analysis methods. Project II will spatially- resolve low-frequency (10 KHz to 5MHz( electrical impedance spectra which are sensitive to changes in cellular morphology and function thereby offering new types of contrast mechanisms between normal and pathological breast tissue. Project III will employ propagating electromagnetic fields (0.5-3 GHz) to interrogate breast tissue in order to discriminate breast malignancy based largely on dispersion differences related primarily to tissue water content. Project IV will use near infrared photon diffusion from multi-spectral illumination of the breast as a vehicle for imaging inherent optical property contrast and functional information on tissue hemoglobin concentration, percent oxygenation and water content as predictors of pathology. Computational, Clinical and Administrative Core units serve to bond these four project components through the programmatic themes of (i) deploying breast imaging adjuncts in a common cohort of patients, (ii) realizing physical property based tissue imaging strategies which offer new types of contrast mechanisms and functional information to aid clinical diagnosis, and (iii) exploiting model-based image reconstruction technologies to quantitatively recovery the electromechanical properties of interest.